Our studies have focused on cell medicated immune responses to two of the retroviruses causing disease in man, namely human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-l). We have demonstrated that chronic infection with HIV-1 may result in high levels of circulating cytotoxic T cells (CTL) in freshly separated peripheral blood mononuclear cells (PBMCs) of healthy seropositive donors. In HTLV-1 infected patients with the neurological disorder tropical spastic paraparesis (TSP), high levels of virus-specific CTL are found both in the PBMC and cerebrospinal fluid (CSF). These CTL are CD8+ and MHC-Class I restricted. CTL to HTLV-L in patients with TSP are predominantly directed against the regulatory protein tax. Using limiting dilution cloning techniques and mitogenic stimulation, we have generated HIV-1 and HTLV-1 specific CTL clones. We have mapped two new CTL epitopes within HTLV-1 tax with synthetic peptides, the first CD8+ CTL epitopes reported to HTLV-1. We have identified the amino acids within two CTL epitopes of HIV-1 and HTLV-1 that are important for binding to major histocompatability complex-Class I proteins and recognition by the T cell receptor. We have identified HTLV-1 in autopsy tissue from the central nervous system of patients with TSP by in situ hybridization. We have shown that CTL to HIV-1 and HTLV-1 can inhibit viral replication or expression of viral proteins. We have found that an HIV-1 specific clone transferred to severe combined immunodeficient mice (SCID) reconstituted with human cells can impede replication of HIV-1 in some animals. We have shown that HIV-specific CTL clones can be activated with a specific peptide antigen to induce calcium influx, and mRNA transcription, protein production, and release of tumor necrosis factor and interferon-gamma.